基于库欣病模型的长期高浓度皮质醇暴露对免疫炎症反应和微生物-肠-脑轴的作用研究  

Research on the effects of long-term exposure to high cortisol concentrations on immune-inflammatory responses and microbiota-gut-brain axis based on a model of Cushing's disease

作　　者：许军鹏 张艳阳[1] 周涛[1] 王鹏[1] 冯哲斌 尚国松 孙宇翔 毛之奇[1] 余新光[1] 张剑宁 XU Junpeng;ZHANG Yanyang;ZHOU Tao;WANG Peng;FENG Zhebin;SHANG Guosong;SUN Yuxiang;MAO Zhiqi;YU Xinguang;ZHANG Jianning(Department of Neurosurgery,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Department of Neurosurgery,The 942nd Hospital of Joint Logistics Support Force of Chinese People's Liberation Army,Yinchuan 750000,China;Department of Neurosurgery,Affiliated Hospital of Hebei University,Baoding 071002,China)

机构地区：[1]解放军总医院第一医学中心神经外科医学部,北京100853 [2]解放军联勤保障部队第九四二医院神经外科,宁夏银川750000 [3]河北大学附属医院神经外科,河北保定071002

出　　处：《空军军医大学学报》2025年第3期344-348,356,共6页Journal of Air Force Medical University

基　　金：科技部科技创新2030“脑科学与类脑科学”重大项目(2021ZD0200407);国家自然科学基金(82001798,81871087);解放军总医院“3+1”青年科技英才培育项目(20230403)。

摘　　要：目的以库欣病(CD)患者为模型,探讨长期高浓度皮质醇暴露对人体炎症反应及微生物肠脑轴的作用。方法前瞻性纳入解放军总医院2021年5月至2024年3月拟手术的16例CD患者,同期匹配健康对照(HC)30名,比较两组患者神经心理学和认知功能评分、炎症因子及肠道菌群的差异。结果研究结果显示CD患者的病程平均为(55.75±39.96)个月,血清皮质醇、促肾上腺皮质激素水平、24 h尿皮质醇排泄量和体质量指数显著高于HC组(P<0.05)。神经心理和认知功能量表数据表明CD患者抑郁自评量表和焦虑自评量表评分显著高于HC组,而简易智力状态检查和蒙特利尔认知评估评分低于HC组(P<0.0001);CD患者与HC组在肠道微生态结构上的差异,包括微生物多样性下降和物种、属水平上的显著不同;通过血液和免疫学指标分析显示,CD患者的白细胞计数、中性粒细胞比例、NLR、IL-1β和IL-8水平较高,而嗜酸粒细胞比例较低(P<0.05),IL-6和TNF水平无显著差异。结论高浓度皮质醇会增加肥胖风险,引起焦虑和抑郁,降低认知功能。除此之外,还会引起炎症反应,降低免疫功能和导致肠道微生物组成结构的改变以及多样性下降。Objective To explore the effects of long-term exposure to high cortisol concentrations on human inflammatory response and microbiota-gut-brain axis by using Cushing's disease(CD)as a model.Methods We prospectively included 16 CD patients who were to be operated from May 2021 to March 2024 in the Chinese PLA General Hospital,and recruited 30 healthy controls(HC)during the same period.We compared the differences in neuropsychological and cognitive function scores,inflammatory factors,and gut microbiota between the two groups.Results Our study results showed that the average course of disease of CD patients was(55.75±39.96)months,and the levels of serum cortisol,adrenocorticotropic hormone,24-hour urinary cortisol excretion,and body mass index were significantly higher than those in HC group(P<0.05).Neuropsychological and cognitive function scale data showed that the scores of Self-Rating Depression Scale and Self-Rating Anxiety Scale in CD patients were significantly higher than those in HC group,while the scores of Mini-Mental State Examination and Montreal Cognitive Assessment were lower than those in HC group(P<0.0001).The differences in gut microbial ecology structure between CD patients and HC group included decreased microbial diversity and significant differences at the species and genus levels.Analysis of blood and immunological indicators showed that the white blood cell count,neutrophil proportion,NLR,and levels of IL-1βand IL-8 in CD patients were higher,while the eosinophils proportion was lower(P<0.05),and the levels of IL-6 and TNF were not significantly different.Conclusion High cortisol concentrations can increase the risk of obesity,cause anxiety and depression,and reduce cognitive function.In addition,it can also cause inflammatory responses,reduce immune function,and lead to changes in the composition and structure of gut microbiota and decreased diversity.

关 键 词：皮质醇 库欣病 肠道菌群 炎症反应 神经心理 下丘脑垂体肾上腺轴 微生物肠脑轴 

分 类 号：R586[医药卫生—内分泌]